Abstract: Acute pancreatitis is a potentially lethal disorder characterized by inflammation and apoptosis of paren­chymal cells. Repeated acute pancreatitis results in chronic pancreatitis and is the major risk factor for pancreatic cancer. Current therapeutic approaches focus on anti-inflammatory and anti-apoptotic. However, the molecular mechanisms that lead to apoptosis and pathogenesis in acute pancreatitis remain unclear. Here, in the current study, we developed a novel approach that using exosomes from mesenchymal stem cells that overexpress Klotho reversed apoptosis, nuclear factor-kB activation in caerulein-stimulated AR42J cells. Klotho attenuated the severity of pancreatic inflammation after caerulein treatment. In conclusion, our results provide evidence that Klotho is a potential therapeutic target for clinical interventions towards acute pancreatitis.